Category: Nevin Manimala

Cannabis Cannabinoid Res. 2021 May 11. doi: 10.1089/can.2021.0014. Online ahead of print.

ABSTRACT

Background: Beside others, neuroinhibitory and sedative effects of CBD were documented. Aim and Methods: The aim of the study was to assess the dose-related effects of CBD premedication on the course of isoflurane anesthesia. Wistar rats were pretreated with different doses of CBD 1 h before isoflurane anesthesia. In the pretreatment, animals were given CBD at doses of 100, 20, 10, or 2 mg kg^-1. Before the fifth (control) anesthesia, the animals were given only mid-chain triglyceride oil, which served as a solvent in the CBD formulation. The induction time was determined, and on awakening, the time to appearance of the flexion reflex and the recovery from anesthesia were determined. Results: Statistical analysis showed a significantly shorter induction time if animals were pretreated with 20 mg kg^-1 CBD. In addition, pretreatment with 100 mg kg^-1 CBD resulted in a prolonged induction time, while on awakening, delayed appearance of reflexes and prolonged recovery from anesthesia compared to pretreatment with 20 mg kg^-1 CBD were observed. Conclusions: The results indicate that the influence of CBD on the course of isoflurane anesthesia depends on the dose and can reduce the induction time. Although this study was performed in laboratory rats, in clinical practice, these data should be considered when CBD-treated patients undergo isoflurane anesthesia.

PMID:33998903 | DOI:10.1089/can.2021.0014

Cannabis Cannabinoid Res. 2021 Apr 16. doi: 10.1089/can.2020.0107. Online ahead of print.

ABSTRACT

Background: The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues. However, no study has investigated differential expression of the endocannabinoid system in labor. Objectives: The purpose of this study was to identify and quantify two components of the endocannabinoid system, the CB₁ cannabinoid receptor and cannabinoid receptor interacting protein 1a (CRIP1a) in uterine and placental tissues, and to determine if there is differential expression in tissues exposed to labor. We hypothesized that CB₁ cannabinoid receptor concentration would be altered in uterine and placental tissue exposed to labor compared with tissues not exposed to labor. Study Design: Uterine and placental tissue samples were collected in nine laboring and 11 nonlaboring women undergoing cesarean delivery. CB₁ cannabinoid receptor and CRIP1a presence and quantification were evaluated using western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Statistical comparisons of laboring and nonlaboring subjects were made for uterine and placental tissue using a Mann-Whitney test. Results: Immunohistochemistry demonstrated positive staining for CB₁ cannabinoid receptors and CRIP1a in uterine tissue. The protein abundance of CB₁ cannabinoid receptor in uterine tissue was significantly lower in tissues exposed to labor (p=0.01). The protein abundance of CRIP1a was lower in uterine tissue exposed to labor but did not reach statistical significance (p=0.06). mRNA expression of CB₁ cannabinoid receptor (p=0.20) and CRIP1a (p=0.63) did not differ in labored compared with nonlabored uterine tissues. Conclusions: Our findings of diminished protein density of CB₁ cannabinoid receptor in uterine tissue exposed to labor support the hypothesis that the endocannabinoid system plays a role in parturition. Our data add to the growing body of evidence indicating the endocannabinoid system is of importance for successful reproduction and support the need for additional research investigating this complex system as it pertains to labor. ClinicalTrials.gov ID: NCT03752021.

PMID:33998898 | DOI:10.1089/can.2020.0107

Cannabis Cannabinoid Res. 2020 Aug 21. doi: 10.1089/can.2019.0095. Online ahead of print.

ABSTRACT

Introduction: Cannabis smoke contains carcinogens similar to tobacco, in addition to compounds with antitumor activity. Cannabis use reduces the risk of obesity and cannabinoids inhibit chronic inflammation, known causes of cancer. The net effect of Cannabis use on cancer risk is not known. Objective: To examine the association between Cannabis use and cancer risk in the United States. Methods: Identify and analyze published data on cancer risk in Cannabis users. Results: A total of 55 data points, consisting of risk ratios of cancer in Cannabis users and nonusers, were identified from 34 studies. Of these, 5 did not contain data essential for inclusion in the meta-analysis. The remaining data showed a nonsignificant trend to an association with reduced risk (relative risk [RR]=0.90, p>0.06, N=50) although heterogeneity is high (I²=72.4%). Removal of data with high risk of selection bias (defined as those from North Africa and those that failed to adjust for tobacco) and data with high risk of performance bias (defined as those with fewer than 20 cases or controls among Cannabis users) resulted in an RR <1.0 (RR=0.86, p<0.017, N=24) and large effect size (Hedges g=0.66), but did not decrease heterogeneity (I²=74.9). Of all cancer sites, only testicular cancer showed an RR value >1, although this was not significant and had a negligible effect size (RR=1.12, p=0.3, Hedges g=0.02). Following removal of testicular cancers the remaining data showed a decrease in risk (RR=0.87, p<0.025, N=41). Cancers of the head and neck showed a negative association with cancer risk (RR=0.83, p<0.05), with a large effect size (Hedges g=0.55), but high heterogeneity (I²=79.2%). RR did not reach statistical significance in the remaining cancer site categories (lung, testicular, obesity-associated, other). The data are consistent with a negative association between Cannabis use and nontesticular cancer, but there is low confidence in this result due to high heterogeneity and a paucity of data for many cancer types.

PMID:33998861 | DOI:10.1089/can.2019.0095

Cannabis Cannabinoid Res. 2021 Feb 11. doi: 10.1089/can.2020.0087. Online ahead of print.

ABSTRACT

Background: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders. Its pathophysiology is diverse and variable, involving disturbed gut-brain interactions, altered motility and secretion, visceral hypersensitivity, increased intestinal permeability, immune activation, and changes in gut microbiota. Complaints experienced by patients suffering from IBS and its co-morbidities strongly impair quality of life (QoL), and available treatments are often unsatisfactory. Anecdotal reports and preclinical data suggest that the endocannabinoid system and functionally related mechanisms could offer treatment targets. Cannabidiol (CBD) is a candidate agent of interest with a broad molecular target profile and the absence of psychoactive properties. Materials and Methods: In 32 female IBS patients, we explored the effect of a chewing gum formulation containing 50 mg CBD on abdominal pain and perceived well-being in a randomized, double-blinded, placebo-controlled cross-over trial. Chewing gums were used on-demand guided by pain symptoms with a maximum of six per day. Pain intensity was assessed by a visual analogue scale (scale 0.0-10.0), and QoL was evaluated with the IBS-36 questionnaire. Results: There was no statistically significant difference in pain scores between CBD and placebo at a group level. Subgroup and individual analyses showed a highly variable picture. No indications were found for symptom-driven intake, which also remained lower than expected overall. Conclusions: With the current design, based on the assumption that IBS patients would adjust their intake to their perceived symptom relief, no differences at the group level were found between CBD and placebo gum in pain scores and the number of gums used. The low use of the gums also indicates that the benefits experienced by these patients generally did not outweigh practical disadvantages such as prolonged chewing throughout the day. The very high intra- and inter-individual variation in IBS symptoms warrant future trials that are more personalized, for example by applying an N-of-1 (rotating) design with individualized dose titration.

PMID:33998882 | DOI:10.1089/can.2020.0087

Cannabis Cannabinoid Res. 2021 Feb 15. doi: 10.1089/can.2020.0133. Online ahead of print.

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the United States. Due to the ongoing legalization of cannabis, its acceptance, availability, and use in the in-patient population are on the rise. In this retrospective study, we investigated the association of cannabis use with important outcomes in COPD hospitalizations. Methods: The National Inpatient Sample (NIS) data were analyzed from 2005 to 2014. The primary outcome of interest was the trends and outcomes of cannabis use among COPD hospitalizations, including in-hospital mortality, pneumonia, sepsis, and respiratory failure. Results: We identified 6,073,862 hospitalizations, 18 years of age or older, with COPD using hospital discharge codes. Of these, 6,049,316 (99.6%) were without cannabis use, and 24,546 (0.4%) were admitted with cannabis use. The majority of COPD hospitalizations with cannabis use were aged 50-64 (60%). Cannabis use was associated with lower odds of in-hospital mortality (odds ratio [OR] 0.624 [95% confidence interval (CI) 0.407-0.958]; p=0.0309) and pneumonia (OR 0.882 [95% CI 0.806-0.964]; p=0.0059) among COPD hospitalizations. Cannabis use also had lower odds of sepsis (OR 0.749 [95% CI 0.523-1.071]; p=0.1127) and acute respiratory failure (OR 0.995 [95% CI 0.877-1.13]; p=0.9411), but it was not statistically significant. Conclusions: Among hospitalized patients with a diagnosis of COPD, cannabis users had statistically significant lower odds of in-hospital mortality and pneumonia compared to noncannabis users. The association between cannabis use and these favorable outcomes deserves further study to understand the interaction between cannabis use and COPD.

PMID:33998884 | DOI:10.1089/can.2020.0133

J Manag Care Spec Pharm. 2021 May 17:1-14. doi: 10.18553/jmcp.2021.21060. Online ahead of print.

ABSTRACT

BACKGROUND: Migraine is a common neurological disease that can have a substantial impact on patients’ lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. OBJECTIVE: To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. METHODS: This retrospective US claims analysis (Optum’s deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. RESULTS: Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; P = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; P < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; P < 0.0001). CONCLUSIONS: In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. DISCLOSURES: This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians’ Education Resource, Rockpointe, ScientiaCME, WebMD/Medscape. The abstract and poster of these results were presented at The Migraine Trust Virtual Symposium (MTIS), October 3-9, 2020.

PMID:33998825 | DOI:10.18553/jmcp.2021.21060

Clin Nurs Res. 2021 May 17:10547738211014211. doi: 10.1177/10547738211014211. Online ahead of print.

ABSTRACT

The purpose of this descriptive study was to describe family caregivers’ experiences and changes in caregiving tasks and approaches during the COVID-19 pandemic. Using web-based strategies, 69 family caregivers of adults with chronic or disabling conditions were recruited and completed an online survey about positive and negative caregiving experiences, and ways in which caregiving has changed. Data were analyzed using descriptive statistics (structured questions) and conventional content analysis (open-ended responses). Participants reported concerns about their loved one’s physical and mental health, the limited access to other caregiving sources, and the limited opportunities to maintain personal well-being. Caregiving tasks completed more than usual included providing emotional support, shopping for groceries and essentials, and contacting healthcare providers. Participants modified their caregiving approach by assuming added responsibilities, leveraging technology, and managing a new caregiving routine. Findings indicate that family caregivers experienced additional caregiving challenges and changed caregiving tasks considering the limited resources available.

PMID:33998836 | DOI:10.1177/10547738211014211

Comput Methods Biomech Biomed Engin. 2021 May 17:1-13. doi: 10.1080/10255842.2021.1925887. Online ahead of print.

ABSTRACT

Electromyography (EMG)-driven neuromusculoskeletal modeling (NMSM) enables simulating the mechanical function of multiple muscle-tendon units as controlled by nervous system in the generation of complex movements. In the context of clinical assessment this may enable understanding biomechanical factor contributing to gait disorders such as one induced by Parkinson’s disease (PD). In spite of the challenges in the development of patient-specific models, this preliminary study aimed at establishing a feasible and noninvasive experimental and modeling pipeline to be adopted in clinics to detect PD-induced gait alterations. Four different NMSM have been implemented for three healthy controls using CEINMS, an OpenSim-compatible toolbox. Models differed in the EMG-normalization methods used for calibration purposes (i.e. walking trial normalization and maximum voluntary contraction normalization) and in the set of experimental EMGs used for the musculotendon-unit mapping (i.e. 4 channels vs. 15 channels). Model accuracy assessment showed no statistically significant differences between the more complete model (non-clinically viable) and the proposed reduced one (clinically viable). The clinically viable reduced model was systematically applied on a dataset including ten PD’s and thirteen healthy controls. Results showed significant differences in the neuromuscular control strategy of the PD group in term of muscle forces and joint torques. Indeed, PD patients displayed a significantly lower magnitude on force production and revealed a higher amount of force variability with the respect of the healthy controls. The estimated variables could become a measurable biomechanical outcome to assess and track both disease progression and its impact on gait in PD subjects.

PMID:33998843 | DOI:10.1080/10255842.2021.1925887

Int J Ment Health Nurs. 2021 May 17. doi: 10.1111/inm.12878. Online ahead of print.

ABSTRACT

Literature shows that mental healthcare workers in Ghana face incessant fear of patient violence that compromise safe care delivery. However, the nature, scale, perceived causes, and consequences of these assaults and how they shape risk perceptions have received limited empirical attention, hence the need for this study. The study employed sequential explanatory mixed methods where questionnaire administration preceded and informed the design of an interview guide used for in-depth interviews with health workers in referral psychiatric hospitals. Descriptive statistics and multivariate logistic regressions were used to analyze the quantitative data. Qualitative data were transcribed and analyzed thematically. Findings showed that physical and non-physical violent assaults and risk perceptions of the hospitals were statistically and significantly associated with females (P < 0.01), nurses (P < 0.01), other clinical cadre (P < 0.01), and those with low job tenure (P < 0.05). About 57% and 71% of the sample reported experiencing physical and non-physical assaults, respectively. Major and minor injuries and psychosocial problems were frequent sequelae following physical violent assaults. As a result, 80% of the participants perceived the hospitals environment to be unsafe to provide care. Violent assaults compromises safety and care delivery efforts suggesting the need for systematic interventions to minimize mental healthcare workers exposure to patient violence.

PMID:33998754 | DOI:10.1111/inm.12878

Orthod Craniofac Res. 2021 May 17. doi: 10.1111/ocr.12494. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy of lingual orthodontics by comparing setups and post-treatment casts.

SETTING AND SAMPLE POPULATION: Thirty-two consecutive patients treated with a customized lingual orthodontic appliance were included in this retrospective study.

MATERIALS AND METHODS: Initial casts, post-treatment casts and setups were scanned, and the digital models produced were analysed in terms of overjet; overbite; molar and canine relationships; intercanine, interpremolar and intermolar distances; upper and lower arch lengths; midline deviation; bucco-lingual angulation of all teeth and mesio-distal angulation of anterior teeth. Comparisons between setups and post-treatment casts were performed via paired t-tests. Relationships between the planned and actual correction were studied using regression analysis.

RESULTS: Statistically significant differences in bucco-lingual torque between setups and post-treatment casts were found for all upper teeth, except for central incisors. In the lower jaw, statistically significant differences in bucco-lingual torque were found between setups and post-treatment casts for the lower incisors and molars. No statistically significant differences in mesio-distal angulation of anterior teeth were found between setups and post-treatment casts. Upper and lower arch widths did not vary significantly between setups and final casts, except upper inter-second premolar and intermolar distances.

CONCLUSION: Customised lingual appliances offer efficient control of mesio-distal angulation of all anterior teeth. Significant differences in torque between setups and post-treatment casts were observed for upper lateral incisors, canines, premolars, and molars, as well as lower incisors and molars. However, the torque difference was clinically significant (over three degrees) for upper second premolars and molars only.

PMID:33998771 | DOI:10.1111/ocr.12494